The liver is the most common site for tumours, which may be cither primary or secondary (metastases). In the Western world hepatic tumours usually represent metastatic disease. The main cause of death for patients with colorectal cancer (incidence: about new 6000 cases in Sweden in 2004) is the presence of liver metastases, which affect about half of these patients. Breast cancer is the most common cancer in women with 6900 new cases in Sweden in 2004. Prostate cancer is the most common cancer in men with a current incidence of 9900 patients/year in Sweden. Lung cancer is the third most common cancer in Sweden, with 3200 new cases each year. Cancer of the pancreas accounts for about 2% of new cancer (900 new cases in Sweden in 2004) but has a poor prognosis. The relative 10-year survival rate is 1.3% for women and 1.5% for men. It is particularly important to find a better therapy for this disease. The above-mentioned cancers are examples of solid tumours that are suitable for interstitial thermotherapy.
Therapy of Solid Tumours
Standard Treatments.
Surgical resection is the mainstay of treatment with curative intent and is combined with adjuvant chemotherapy in diseases for which cytostatic drugs have a demonstrable effect. Chemotherapy is the sole treatment when the aim of treatment is palliative. Cytostatic drugs are usually given systemically via the intravenous or oral routes but may also be given regionally via intra-arterial infusion. Irradiation seems to be inferior to surgical resection with regard to local efficacy.
Minimally Invasive Therapies, Including Local Destruction Methods.
Some methods, like radiofrequency ablation (RFA), laser-induced hyperthermia, cryotherapy and percutaneous ethanol injection (PEI) have been used rather extensively. Others like microwave coagulation or photodynamic therapy, have been used less often in patients with solid tumours. Some, like electrochemotherapy or high intensity focused ultrasound, arc being developed.
As compared to surgical resection, the advantages of local tumour destruction include a) selective tissue damage which leads to a smaller immunosuppression and a smaller release of growth factors, b) minimal treatment morbidity and mortality, and c) the possibility to use chemotherapy in a more efficient way since chemotherapy can be started before or at the time of local therapy.
Interstitial Laser Hyperthermia
Interstitial laser hyperthermia is a thermal technique, which destroys tumours by absorption of light. Early experimental and clinical studies used an Nd-YAG laser and bare fibres inserted into the centre of a tumour, which created lesions that were 1.5 cm in diameter or less. It was soon apparent that clinical application would require larger lesions and improved control of the tissue effect. Methods to improve lesion size included multi-fibre systems, diffuser type fibres and vascular inflow occlusion. However the standard application of interstitial laser hyperthermia results in evaporisation and carbonisation of tissue and relatively unpredictable tissue damage and lesion size. This has led to the development of feedback control systems that monitor temperature within tissue by means of temperature sensors placed at various distances from the point of treatment and which are interfaced with a computer and a laser. The idea of these systems is that the laser output is adjusted to return the monitored temperature to the desired temperature level when the monitored temperature rises above a set temperature or falls beyond a set temperature. It is thus possible to maintain a substantially constant temperature over a desired period of time at the measuring points which surround a known volume of tissue, which is intended to give a high degree of precision with respect to both lesion size and type of cellular damage.
One of the advantages of feedback control of the treatment effect is that it ensures reproducible and cytotoxic temperatures in the periphery of tumour tissue. Another way to control lesion size is to use a dose planning system, which enables lesion size to be calculated for different tissues, output powers and treatment durations. Planning of local treatment can also be integrated with computer aided image analysis to give information about the size and location of tumours, vessels and bile ducts in 3-D views.
However such methods only determine the temperature in the vicinity of the temperature sensor(s) and give no information on whether the required temperature has been achieved throughout the tissue that is supposed to be treated.
Interstitial Laser Thermotherapy (ILT)
Interstitial laser thermotherapy (ILT) is a variant of interstitial laser hyperthermia where the focus is on killing tumour cells at temperatures of 46-48° C., i.e. at temperatures that do not cause tumour antigens to coagulate. Consequently ILT eventually produces cell death while still allowing the presentation of intact tumour antigens. These cause an inflammatory local reaction and this can produce an efficient immune response, both in rats and in human patients. This is in contrast to ablative techniques that use higher temperatures and thus cause instantaneous necrotisation of the tissue. This is also in contrast to traditional hyperthermia that uses significantly lower temperatures, i.e. <42.5° C., and long exposure times.
For feedback control of the laser power one or more thermometers (thermistors or thermocouples) placed within the tumour and/or at the tumour boundary have commonly been used. One of the disadvantages with this type of monitoring is that it requires interstitial positioning of probes and thus additional preparations. It is advantageous to encase the monitoring device, e.g., a thermistor probe, with the laser fibre close to the laser tip, avoiding separate punctures for temperature measurement.
A problem that has occurred during feedback control using thermometers is that they only measure the local temperature and are unable to detect if overheating (or insufficient heating) occurs in tissue which is not close to the thermometer. Overheating is undesirable as it may lead to carbonisation and/or necrotic breakdown of the tissue. Carbonisation may be present as a black layer surrounding the heat source which layer impairs light penetration and reduces the distance that light can propagate in the tissue. Rapid necrotic breakdown can cause poisoning. Insufficient heating is undesirable as it leads to ineffective treatment of the tissue. Attempts to determine changes in the electrical properties of tissue caused by heating have used implanted leads provided with electrodes to measure the impedance or transfer properties of the tissue and thermistors or thermocouples to measure temperature—tissue impedance thermography. Using different frequencies for the current used in impedance measurements it is possible to measure impedances in tissue local to the measuring electrodes as well as tissue further away. However the results have hitherto been considered unreliable as the values of the impedance or transfer property obtained when the temperature readings reach an elevated steady state (i.e. a constant temperature, for example 46° C.) have changed continuously in such a way that it appears that they are drifting—see FIG. 4 and FIG. 5. These figures show temperature and impedance against time at three distances from the laser tip. Both graphs have a similar pattern showing that changes in the measured tissue properties, in this case the measured impedance, follow changes in the tissue temperature, and that an irreversible change in the impedance occurs such that the impedance at, for example, 40° C. at the beginning of the experiment is not the same as the impedance at 40° C. at the end of the heating phase. Similarly FIG. 6, which shows conductance against temperature for a tumour using information gathered from the experimental results shown in FIG. 2 “Conductance versus temperature at 44 kHz and 1 MHz for an EMT6 tumour in vivo” in “The effect of hyperthermia-induced conductivity changes on electrical impedance temperature mapping,” M. A. Esrick, D. A. McRae, Phys. Med. Biol. 39 (1994) 133-144, shows that the conductance of EMT6 tumour tissue in vivo while being heated from 37° C. to 45/46° C. over a period of 19 minutes varies substantially linearly. From this figure it is possible to determine that the conductivity of this tissue at a current frequency of 44 kHz and 37° C. is around 3.5 mS, at 46° C. it is around 3.85 mS. Looking at this limited range the thermal coefficient is 0.038 mS/° C. when measured at 44 kHz. When measured at 1 MHz the conductivity at 37° C. is around 5.152 mS, at 45° C. it is around 5.8 mS. Looking at this limited range the thermal coefficient is 0.081 mS/° C. when measured at 1 MHz.
Cancer Therapy Using Laser Devices
Mueller et al. (DE 3931854, 1991) presented an invention based on an MRI tomograph for tumour location and monitoring during interstitial laser irradiation of tumours, e.g., in the liver, via quartz light conducting fibres. The invention was said to relieve the patient from surgery, long hospitalisation and to enable tumour removal with small side effects for the patient. In this invention a multiplanar x-ray device is coupled to the MRI tomograph to enable the fibres to be placed in the tumour using point ion probes and the coordinates of the tumour to be determined by MRI tomography.
When performing an interstitial heat treatment of cancer tumours a feedback system that is able to present information to the user regarding the progress and outcome of the treatment is crucial. In prior art devices and methods, treatment is often performed based on experience collected during previous treatments and the session time is set based on this knowledge. As a secondary means for treatment control, the tissue temperature may be monitored at a limited number of measurement points. In many cases the treatment time is set to a period longer than that which is actually required as reliable means for feedback regarding how the tissue is responding to the heating, the “tissue effects,” do not exist. For the same reason the desired result cannot be obtained in many cases as the temperature distribution is not uniform in the target area and proper positioning of the temperature sensors cannot be ensured. As a temperature sensor can only sense the local temperature there is no way of checking if there are cold spots outside the local area, such cold spots being caused, for example, by blood vessels passing through the tissue and conducting away the heat.